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http://purl.uniprot.org/citations/25393644http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/25393644http://www.w3.org/2000/01/rdf-schema#comment"

Context and objective

11β-hydroxysteroid dehydrogenase type 1 (11βHSD1) catalyses regeneration of cortisol in liver, adipose tissue, and skeletal muscle, making a substantial contribution to circulating cortisol as demonstrated in humans by combining stable isotope tracer infusion with arteriovenous sampling. In the brain, 11βHSD1 is a potential therapeutic target implicated in age-associated cognitive dysfunction. We aimed to quantify brain 11βHSD1 activity, both to assess its contribution to systemic cortisol/cortisone turnover and to develop a tool for measuring 11βHSD1 in dementia and following administration of 11βHSD1 inhibitors.

Design, setting, and participants

With ethical approval and informed consent, 8 healthy men aged 38.1 years (sd 16.5) underwent an ECG-gated phase-contrast magnetic resonance scan to quantify internal jugular vein blood flow and were infused with 1,2 [(2)H]2-cortisone and 9,11,12,12 [(2)H]4-cortisol for 3 h before samples were obtained from the internal jugular vein and an arterialized hand vein. Steroids were quantified by liquid chromatography-tandem mass spectrometry.

Main outcome measures and results

Steady state tracer enrichments were achieved and systemic indices of cortisol/cortisone interconversion were consistent with previous studies in healthy men. However, there was no measurable release or production of cortisol, 9,12,12 [(2)H]3-cortisol or cortisone into the internal jugular vein.

Conclusions

Although cerebral 11βHSD1 reductase activity may be greater in cognitively impaired patients, in healthy men any contribution of 11βHSD1 in the brain to systemic cortisol/cortisone turnover is negligible. The influence of 11βHSD1 in the brain is likely confined to subregions, notably the hippocampus. Alternative approaches are required to quantify pharmacodynamics effects of 11βHSD1 inhibitors in the human brain."xsd:string
http://purl.uniprot.org/citations/25393644http://purl.org/dc/terms/identifier"doi:10.1210/jc.2014-3277"xsd:string
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/author"Semple S."xsd:string
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/author"Marshall I."xsd:string
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/author"Andrews P."xsd:string
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/author"Andrew R."xsd:string
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/author"Walker B.R."xsd:string
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/author"Kilgour A.H."xsd:string
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/date"2015"xsd:gYear
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/name"J Clin Endocrinol Metab"xsd:string
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/pages"483-489"xsd:string
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/title"11beta-Hydroxysteroid dehydrogenase activity in the brain does not contribute to systemic interconversion of cortisol and cortisone in healthy men."xsd:string
http://purl.uniprot.org/citations/25393644http://purl.uniprot.org/core/volume"100"xsd:string
http://purl.uniprot.org/citations/25393644http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/25393644
http://purl.uniprot.org/citations/25393644http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/25393644
http://purl.uniprot.org/uniprot/#_P28845-mappedCitation-25393644http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25393644
http://purl.uniprot.org/uniprot/#_X5D2L1-mappedCitation-25393644http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/25393644
http://purl.uniprot.org/uniprot/P28845http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/25393644
http://purl.uniprot.org/uniprot/X5D2L1http://purl.uniprot.org/core/mappedCitationhttp://purl.uniprot.org/citations/25393644